The spine is a remarkably strong and flexible structure that is capable of withstanding substantial forces. A spine is formed from a plurality of vertebrae, each of which is individually separated from the other by a disc. The discs are anterior to the spinal cord, which runs through the spinal canal of the vertebrae. The discs have several functions, one of which includes serving as shock absorbers for the vertebrae.
Each disc has a relatively tough outer layer called the annulus fibrosus that surrounds a gel-like inner layer called the nucleus pulposus. The annulus fibrosis is composed of concentric layers of intertwined annular bands, which are arranged to resist forces placed upon the spine. The cartilaginous endplate separates the nucleus pulposus and annulus fibrosus from the adjacent vertebrae. The posterior longitudinal ligament strongly attaches to the annulus fibrosus. The nucleus pulposus is composed of cells from the primitive notochord in childhood and chondrocyte-like cells in adulthood, and contains significant amounts of substances capable of exciting, or increasing the excitability of, sensory nerves. These substances include prostaglandin E, histamine-like substances, potassium ions, lactic acid, and several polypeptide amines.
Pain arising from the disc or elements adjacent to an intervertebral disc may cause axial pain also called discogenic pain with or without a radiculopathy component. Generally, though not always, to experience pain in a particular region the presence of nerve endings in that region is required. One source of pain is caused by the activation of specific nociceptors connected with C- and A-delta fibers. Another source of pain involves injury to sensory fibers, or damage to the central nervous system. Alternatively, abnormal interactions between neuronal extensions of sensory and autonomic nature can also be involved in symptomatic pain. Hence, the innervation of the disc and elements adjacent to an intervertebral disc is of interest to the study of discogenic pain.
Neuronal extensions innervating the disc and region adjacent to the disc are of motor, sensory or autonomic nature. Normal discs are rarely innervated deeper than the outer third of the annulus fibrosus. However, there are indications that degenerating or problematic discs have nerve extensions that extend centripetally beyond the outer third of the annulus fibrosis, reaching as far as the inner third of the annulus fibrosis, or even into the nucleus pulposus. The invasion of such neuronal extensions may be a source of pain, particularly if they come into contact with those substances in the nucleus pulposus that are capable of exciting such neuronal extensions. Signs of degeneration associated with the development of axial pain with or without radiculopathy such as increasing innervation have also been found in elements adjacent to the disc, for example the endplates.
Discs are generally avascular, with the transport of nutrients and metabolites occurring primarily through diffusion. However, degenerations tend to be more vascular than normal discs. This centripetally invasive vascularization of the disc, analogous to the neuronal invasion, may contain a perivascular nerve network with vasomotor or vasosensory functionalities. Further, increased vascularization of the disc is associated with increased innervation, and hence increased chances for discogenic pain.
A degenerating disc can be a contained disc or a herniated disc and cause discogenic pain also referred to as axial pain with or without radiculopathy. Herniation could be of a contained nature, for example, bulging of the disc. A herniated disc can also be ruptured with release of discal elements, such as the nucleus pulposus, outside the disc. A degenerating disc can affect the surrounding neuronal elements including the spinal nerve roots and cause radicular pain or radiculopathy. Radiculopathy also referred to sciatica or arm or leg pain depending on the level of the spine affected by the degeneration.
Changes in the appearance of the degenerating disc and/or elements adjacent to the disc can be associated with changes in matrix components including changes in density such as increased density of the nucleus pulposus, level and type of extracellular matrix components such as proteoglycans, metalloproteinases and proteolytic enzymes, collagen and fibronectin fragments and content in nitric oxide and free radicals.
Immune elements including pro-inflammatory agents including cytokines, chemokines, growth factors, peptides, polypeptides and nitric oxide synthetase can also be involved in the degenerative process and development of symptomatic pain associated with axial pain with or without radiculopathy clinical conditions.
In a Gallup Survey, 42% of American adults said that they experienced pain on a daily basis. Amongst such sufferers of chronic pain, spine-related problems constitute the bulk of the complaints. Back and leg pain has been estimated to exist in as much as 66% of the general population. Beyond the substantial discomfort that back and leg pain inflicts upon individuals, spine-related pain also incurs heavy social costs. For example, as many as one million spine surgeries, and as many as five million interventional procedures, are estimated to be performed in the United States each year. Well beyond the purely medical and psychological burdens of such procedures, the subsequent social costs related to productivity, disability compensation, and lost taxes, are substantial.
Accordingly, better strategies to diagnose the precise location of the pain generator(s) involved in axial pain conditions with or without radiculopathy are needed in order to increase the effectiveness of therapeutic interventions.
In addition, better strategies to monitor the progression of pathological changes in the disc or adjacent to an intervertebral disc are needed to enable prophylactic treatment before the development of a painful condition.